COX-2 and prostanoid receptors: good targets for chemoprevention.

Accumulating evidence indicates that COX-2 inhibitors are involved in colon and breast cancer development. Our previous studies indicated that nimesulide and celecoxib, selective COX-2 inhibitors, show inhibitory effects of intestinal carcinogenesis in azoxymethane-treated rats and mice and in Min mice models. We recently found that nimesulide suppressed PhIP-induced breast cancer in female SD rats in which COX-2 protein was overexpressed. These results led us to investigate the effects of prostaglandin E2 (PGE2) in the target tissues. PGE2 showed its biological activity through binding to its membrane receptors, EP(1 to approximately 4). We also investigated the effects of EP receptors on colon carcinogenesis. We used receptor knockout mice and selective receptor antagonists. Our results indicated that the EP1 receptor plays a pivotal role in colon carcinogenesis. Selective EP1 receptor antagonists may be a new class of chemopreventive agents against colon cancer.